The objectives of the proposed research are (1) to determine the mechanism(s) whereby ethanol impairs platelet function and survival, (2) to define interactions between ethanol and other drugs with respect to platelet function, (3) to assess the occurrence and severity of platelet damage induced by acidification, (4) to construct a simple assay for antiplatelet antibodies using ethanol-treated and/or acid-treated platelets, and (5) to evaluate alterations in biogenic amine metabolism of platelets induced by ethanol. Mechanisms of ethanol-induced platelet injury will be studied by determining (a) changes in membrane structure and function, (b) adenine nucleotide turnover and release, (c) uptake of C14-serotonin, (d) cyclic AMP levels and adenylate cyclase activity, (e) electron microscopical changes, and (f) glycogenolysis and phosphorylase activity of platelets from patients ingesting ethanol or normal platelets exposed to ethanol in vitro. Interactions of drugs with ethanol and effects of acidification on platelets will be determined in vitro using platelet aggregometry, measurements of C14-serotonin release, and electron microscopy. Antibody assay will be based on platelet aggregometry using ethanol and/or acid to induce mild degrees of platelet damage to produce a sensitive indicator cell. Changes in biogenic amine metabolism will be determined from measurements of C14-serotonin uptake and release, 5-hydroxytryptophan decarboxylase activity, and monoamine oxidase activity. It is hoped that the results of these studies will elucidate how ethanol affects platelets, provide further insight into platelet physiology, offer practical information for the clinician regarding safe drug usage in alcoholics, assess the suitability of current platelet survival methods for use in patients with abnormal platelets, provide a simple antibody assay, and provide insight into mechanisms whereby ethanol affects nerve cells.